Oxidation of Pyrazoline

7/29/2019 Oxidation of Pyrazoline

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Mild Oxidation of 1,3,5-Trisubstituted Pyrazolines with

N-Bromo-sulphonamides

Ramin Ghorbani-Vaghei,* Davood Azarifar and Behrooz Maleki

Department of Chemistry, Faculty of Science, Bu-Ali Sina University, Hamadan, Iran

1,3,5-Trisubstituted pyrazolines to pyrazoles are carried out efficiently in the presence of new reagents

N,N,N,N-tetrabromo-benzene-1,3-disulfonylamine [TBBDA] and N,N-dibromo-N,N-1,2-ethanediylbis-

(p-toluenesulphonamide) [BNBTS] in solvent-free conditions with catalytic amounts of SiO2 under micro-

wave irradiation in high yields.

Keywords: Pyrazolines; Oxidation; Aromatization; BNBTS; TBBDA.

INTRODUCTION

The oxidation of 1,3,5-trisubstituted pyrazolines to

pyrazoles is an important trans formation in organic synth esis

andbecauseof its significantrole, it often has been used com-

mercially for its analgesic, anti-inflammatory, antipyretic,

antiarrhythmic, tranquilizing, muscle relaxant, psychoana-

leptic, anticonvulsant, monoamineoxidase inhibitor, anti-

diabetic and antibacterial activities.1 Therefore, oxidative

aromatization of pyrazolines2 with oxidizing reagents should

provide an efficien t method for the prepara tion of pyrazole

derivatives. For this oxidative conversion of pyrazolines, a

limited number of reports exist in the literature which include

Zr(NO3)4,3 Pd/C,4 Co(II) and oxygen,5 iodobenzene diace-

tate,6 lead tetraacetate,7 MnO2,8 pot ass ium per man gan ate 9

and NBS,10 but most of them suffer from the use of excess re-

agent, longer reaction times, higher temperatures, formation

of side products, solvents and difficulty in removing the re-

agent from the sensitive pyrazoles.

RESULTS AND DISCUSSION

Herein, we report on a simple and efficient procedure

for oxidative aromatization of 1,3,5-trisubstituted pyrazo-

lines to pyrazoles using N,N,N,N-tetrabromo-benzene-1,3-

disulfonylamine [TBBDA] and N,N-dibromo-N,N-1,2-eth-

anediylbis(p-toluenesulphonamide) [BNBTS]11

(Fig. 1) in

solvent-free conditions with catalytic amounts of SiO2 under

microwave irradiation.

The advantages ofBNBTS and TBBDA are as follows:

1. The preparation ofBNBTS and TBBDA are easy.

2. BNBTS and TBBDA are stable for two to three

months under atmospheric conditions.

3. After completion of the reaction, the sulphonamide is

recovered and can be reused many times without decreasing

the yield.

The reaction of 1,3,5-trisubstituted pyrazolines with

BNBTS orTBBDA afforded pyrazoles without side products

(Scheme I).

The results of the conversion of various 1,3,5-trisub-

stituted pyrazolines to their corresponding pyrazoles in the

presence or absence SiO2 are presented in Tables 1 and 2.

It was found that the best result is obtained in the pres-

ence of SiO2 (Tables 1 and 2), because silica absorbed the

microwave radiation and caused enhanced chemical reac-

Journal of the Chinese Chemical Society, 2004, 51, 1373-1376 1373

* Corresponding author. Fax: (+98) 811 8272404; e-mail: [email protected]

S

OO

S

OO

NNH

H

H

H

S

OO

N

CH3

CH2S

OO

S

OO

NN

Br

Br

Br

Br

BNBTS TBBDA

Br

21

)2

S

OO

N

CH3

CH2 )2

H

Fig. 1.


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1374 J. Chin. Chem. Soc., Vol. 51, No. 6, 2004 Ghorbani-Vaghei et al.

BNBTS

N N

RR

Ph

1 2

TBBDA

N N

RR

Ph

1 2

3 4

or

MW

+ 1 or 2Solid phase

Presence SiO2

or

Scheme I

Table 1. Oxidative aromatization of 1,3,5-trisubstituted pyrazolines with BNBTS in solvent-free conditions with

catalytic amounts of SiO2 under microwave irradiation

Substrate Producta R1 R2 Reagent/ProductTime (min)

Ib (II)cYield (%)

Ib (II)c

1a 2a 2-Naphthyl 2-CH3C6H4 4 11 (7) 70 (86)

1b 2b Ph Ph 4 10 (4) 68 (78)1c 2c 4-CH3C6H4 3-CH3C6H4 5 12 (5) 71 (82)

1d 2d 3-CH3C6H4 4-ClC6H4 5 10 (4) 62 (76)

1e 2e 4-OCH3C6H4 Ph 4.25 8 (6) 72 (90)

1f 2f 4-OCH3C6H4 2-CH3C6H4 4.5 14 (5) 70 (90)

1g 2g 4-OCH3C6H4 3-CH3C6H4 4.25 12 (5) 64 (82)

1h 2h 2-Naphthyl 3-CH3C6H4 5 14 (8) 72 (78)

1i 2i 2-Naphthyl 2-ClC6H4 5 11 (7) 66 (78)

1j 2j 2-Naphthyl 4-ClC6H4 5.5 15 (10) 70 (88)

1k 2k 3-CH3C6H4 4-N(CH3)2C6H4 5 11 (5) 64 (88)

1l 2l 4-OCH3C6H4 2-ClC6H4 4.5 14 (6) 58 (73)

a Products were characterized by their physical properties, comparison with authentic samples, and by spectroscopic

methods.b In the absence of SiO2.c In the presence of SiO2 (1 mmol of reagent/0.02 mmol of SiO2).

Table 2. Oxidative aromatization of 1,3,5-trisubstituted pyrazolines with TBBDA in solvent-free conditions with

catalytic amounts of SiO2 under microwave irradiation

Substrate Producta R1 R2 Reagent/ProductTime (min)

Ib (II)cYield (%)

Ib (II)c

1a 2a 2-Naphthyl 2-CH3C6H4 2.75 14 (6) 78 (88)

1b 2b Ph Ph 2.75 12 (4) 75 (82)

1c 2c 4-CH3C6H4 3-CH3C6H4 3.75 14 (5) 80 (90)

1d 2d 3-CH3C6H4 4-ClC6H4 3.5 15 (6) 70 (84)

1e 2e 4-OCH3C6H4 Ph 3 13 (7) 89 (90)1f 2f 4-OCH3C6H4 2-CH3C6H4 3.25 15 (5) 70 (90)

1g 2g 4-OCH3C6H4 3-CH3C6H4 3 14 (6) 72 (84)

1h 2h 2-Naphthyl 3-CH3C6H4 3.75 14 (7) 80 (84)

1i 2i 2-Naphthyl 2-ClC6H4 3.5 12 (4) 72 (88)

1j 2j 2-Naphthyl 4-ClC6H4 4 16 (8) 70 (76)

1k 2k 3-CH3C6H4 4-N(CH3)2C6H4 3.75 14 (7) 72 (82)

1l 2l 4-OCH3C6H4 2-ClC6H4 3 12 (5) 76 (79)

a Products were characterized by their physical properties, comparison with authentic samples, and by spectroscopic

methods.b In the absence of SiO2.c In the presence of SiO2 (1 mmol of reagent/0.014 mmol of SiO2).


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tions.12,13 Of course, this reaction was examined with SiO2 in

the absence ofN-bromosulfonamide, and the progress of the

reaction was not observed.

In conclusion, the presented method is an efficient andselective protocol for aromatization of 1,3,5-trisubstituted

pyrazolines to pyraz oles. Thus, micro wave irradiation could

be used for the oxidation of a wide variety of pyrazoline de-

rivatives with BNBTS and TBBDA in the presence of a cata-

lytic amount of SiO2. Also, the results show that the mole of

SiO2 in TBBDA is approximately 50% that of in BNBTS.

EXPERIMENTAL

IR and NMR spectra were recorded using a Shimadzu435-U-04 spectrophotometer (KBr pellets) and a 90 MHz

Jeol FT-NMR spectrometer, respectively. A Butane Indus-

trial Co. microwave (220 v, 1000 w) was used for the micro-

wave irradiations.

Procedure for preparation of benzene-1,3-disulfonyl-

amide

To benzene-1,3-disulfonyl acid sodium salt (0.016 mol)

was added PCl5 (0.0165 mol) as chlorination agent. For start-

ing the reaction, the vessel should be heated (40-50 C), then

the reaction completes spontaneously. After complete con-version (2 h), crushed ice (100 g) was added; the product was

separated from inorganic materials by chloroform. Then to

the solution was added NH3 (l) (400 mL); the reaction mix-

ture was stirred with a mechanical stirrer. After complete ad-

dition, removal of the solvent under reduced pressure gave

the crude product. The pure product (90%, m.p. 228-230 C)

was obtained by crystallization with ethanol. IR spectrum

(KBr pellets): 3320, 3090, 1600, 1320, 1130 cm-1. 1H NMR

(acetone-d6): d 6.7 (s, 4H),7.7 (t, 1H), 8.1 (d, 2H), 8.3 (s, 1H).13C NMR: 124.2, 130.6, 129.8, 124.2.

Procedure for preparation of N,N,N,N-Tetrabromo-

benzene-1,3-disulfonylamide [TBBDA]

N,N,N,N-Tetrabromo-benzene-1,3-disulfonylamide

(0.003 mol) was dissolved in a slight molar excess of chilled

sodium hydroxide solution (3 M) at room temperature and

was the solution transferred to a beaker. Then bromine

(0.0584 mol) was added to the solution with vigorous stir-

ring, and immediately precipitate was formed. The product

was collected on a buchner funnel, and it was washed with 30

mL distilled cold water and then dried in a vacuum desicator

at room temperature for 6 h. The yield of pure TBBDA, m.p.

267-270d C, was 90%. The reagent was identified by NMR,

IR spectroscopies. IR spectrum (KBr pellets): 3070, 1620,

1310, 1130 cm-1. 1H NMR (acetone-d6): d 7.9 (t, 1H), 8 (d,

2H), 8.3 (s, 1H). 13C NMR spectrum (acetone): d 123.4,128.7, 127.9, 122.3.

General procedure for oxidation of 1,3,5-trisubstituted

pyrazoline with TBBDA or BNBTS

A mixture of 1,3,5-trisubstituted pyrazoline 3 (1

mmol), BNBTS or TBBDA (1 mmol) and SiO2 (0.014-0.02

mmol) was introduced in a flask and was irradiated in a mi-

crowave oven at a power output of 1000 W for the appropri-

ate time as indicated in Tables 1 and 2. After irradiation and

monitoring on TLC (hexan:aceton, 10:1), the product is ex-

tracted with carbon tetrachloride; K2CO3 (0.5 g) was addedand stirred for 0.5 h, and the insoluble sulfonamide 1 or2 was

removed by filtration and washed with cold carbon tetrachlo-

ride (10 mL). Removal of the solvent under reduced pressure

gave the crude product. The pure product 4 was obtained by

recrystalization with methanol/H2O (10:1).

Received February 24, 2004.

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